PROJECT SUMMARY Due to significant advances in the treatment of pediatric cancer patients, the five year survival rate now exceeds 80% in the USA. Among the myriad long-term physical and psychosocial effects of treatment, reproductive dysfunction is reported as a major concern and is highly correlated with quality of life in this population. The etiology of reproductive dysfunction in childhood cancer survivors (CCS) is complex and few predictors of this effect of treatment have been identified. High levels of psychological stress have also been observed in CCS; psychological stress activates the hypothalamic-pituitary-adrenal (HPA) axis, which can suppress hypothalamic-pituitary gonadal function and disrupt reproductive function. The proposed research project will examine ovarian function in survivors of childhood cancer, a population at increased risk of reproductive dysfunction due to late effects of cancer treatment and psychological stress. The specific aims are (aim 1) to explore the relationship between perceived stress, biomarkers of HPA activity, gonadotropin levels, and anti-Mllerian hormone (AMH); and (aim 2) to determine the model that best explains the relationship between the most salient variables identified in aim 1. This cross-sectional cohort study will enroll 50 female patients between the ages of 16 and 35 who were treated for childhood cancer at the Edinburgh Children?s Cancer Centre, Royal Hospital for Sick Children. Perceived stress will be measured using the Perceived Stress Scale-10. HPA activity will be measured using salivary and hair cortisol and salivary IL-6. Ovarian function will be measured using serum gonadotropin levels, serum AMH levels, and menstrual cycle characteristics, which are collected routinely during the subject?s annual follow-up visit. Biological samples will be analyzed using commercially available ELISA kits in the Queen?s Medical Research Institute. For aim 1, data will be analyzed using linear regression models using a best-subset variable selection procedure and aim 2 will employ nonlinear models to determine the model that best explains the relationship between variables identified from the analysis of aim 1.The findings from this study will increase our understanding of AMH as a biomarker of reproductive function, especially ovarian function. The sponsors are experienced mentors and experts in ovarian function (Anderson) and laboratory assessment of biomarkers (McCarthy). While conducting this study, the applicant will attend weekly seminars on reproductive physiology. This training program will prepare the applicicant to conduct cutting edge research on biobehavioral processes affecting ovarian aging.